Von Blume et al. reveal how a calcium-binding protein helps sort secretory cargo at the trans-Golgi network (TGN).

After moving through the secretory pathway from the ER to the Golgi apparatus, proteins are sorted at the TGN for delivery to their final destinations. How soluble proteins are selected for secretion outside of the cell is unclear, though the sorting process appears to rely on an ATPase called SPCA1, which pumps calcium ions into the TGN lumen when activated by the actin-severing protein cofilin. Cells lacking either SPCA1 or cofilin exocytose reduced amounts of many secretory proteins while incorrectly secreting other proteins that are normally retained in the Golgi complex or delivered to lysosomes.

Von Blume et al. found that a calcium-binding Golgi protein called Cab45 helps regulate calcium levels and protein sorting at the TGN. Calcium import through SPCA1 was required to retain Cab45 in the Golgi lumen, and Cab45, in turn, was required to maintain normal calcium levels inside the TGN. Cab45 bound to several secretory proteins in a calcium-dependent manner, and exocytosis of these proteins was inhibited in Cab45’s absence. Lysosomal proteins, on the other hand, were secreted from cells lacking Cab45, suggesting that Cab45 operates in the same sorting pathway as SPCA1 and cofilin.

The researchers now want to identify additional components of the pathway to determine how Cab45 packs secretory proteins into transport vesicles destined for the plasma membrane.

Von Blume
et al
J. Cell Biol.

Author notes

Text by Ben Short